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2 DIET: Studies of dietary influences on Alzheimer's disease do not yet provide clear evidence. Also the number of epidemiologic studies examining dietary effects is limited. Thus, at this time, we cannot say that any particular nutritional component causes or prevents Alzheimer's disease. However, much of the evidence from early studies in many ways reflects a pattern of dietary associations very similar to more established dietary risk factors for heart disease. Thus, patients who adopt dietary practices to reduce their risk for heart disease may also reduce their risk of developing Alzheimer's disease. VITAMINS A AND E: The best evidence of disease prevention relates to antioxidant nutrients, and vitamins E and C. The changes in the brain that are thought to cause Alzheimer's disease include amyloid plaques, and tau tangles within the nerve cells. The end result is disruption of nerve cell functioning leading to nerve cell death. Numerous animal and laboratory studies have shown that Alzheimer's disease involves both oxidative stress and inflammation, although it is not known whether these processes are a cause or effect of the disease or both. The brain is a site of high metabolic activity that generates free radical molecules that are toxic to cells. Infection, cell injury, and environmental toxins, such as smoking and pollution, also generate free radical molecules. The body possesses natural protective mechanisms to combat oxidative stress, including antioxidant proteins and nutrients. Vitamin E is a potent antioxidant that resides within cell membranes, where it can neutralize these toxins as they are generated. Vitamin E also has anti-inflammatory properties. Vitamin C, a less potent antioxidant than vitamin E, circulates within the plasma and retains the additional function of restoring vitamin E to its antioxidant capacity. Animal and laboratory studies demonstrate that the antioxidant nutrients, vitamin E in particular, protect the brain from damage due to oxidative and inflammatory toxicity. Studies in rodents fed antioxidant-supplemented diets had superior learning acquisition and memory retention compared with rodents on control diets. At death, the brains of the antioxidant-fed rodents exhibited less nerve cell loss and less evidence of oxidative damage and inflammation. The vitamin E in dietary supplement pills is a different chemical version from the vitamin E found in fresh food sources. It is believed that fresh food is a far better way to get the protective effects from vitamin E. In summary, the strongest evidence for antioxidant protection against Alzheimer's disease rests with high food intake of vitamin E. The richest food sources of vitamin E include vegetable oils, margarine, nuts (especially almonds), and seeds (especially sunflower seeds). Moderate amounts of vitamin E are found in whole grains, egg yolk, and a limited number of vegetables (eg, collard greens) and fruits (eg, avocados, apples, melons).

3 DIETARY FAT: Although, the biochemical mechanism is not yet identified, cholesterol appears to be an important component in Alzheimer's disease and is involved in both the generation and deposition of beta amyloid protein. In studies of animals fed high-fat and high-cholesterol diets, impaired learning and memory performance was observed and more beta amyloid deposition in the brain, greater loss of nerve cells, and other Alzheimer's disease-related changes. One study in middle-aged men, found that an elevated blood cholesterol level was associated with three times the risk of developing Alzheimer's disease in late life. Two recent studies of patients who had been prescribed statin cholesterol lowering drugs found a significantly lower risk of Alzheimer's disease compared with similar patients who were not prescribed these medications. It is not clear if this reduction in Alzheimer's disease resulted from cholesterol lowering or some other effect of the medication. Other studies in humans, showed that a high intake of saturated fat doubled the risk of Alzheimer's disease, and even moderate intake of trans fat increased the risk by two to three times. By contrast, higher intake of both polyunsaturated and monounsaturated fats was associated with lower risk of developing Alzheimer's disease. Although, there are other human studies, that provide some conflicting results. FISH OIL: Fish oil, is a type of polyunsaturated fat derived from fish. One of the fats called, docosahexaenoic acid (DHA,) is the primary component of nerve cell membranes and is particularly abundant in the more very active areas of the brain. These fats are important in early brain development. DHA and a similar fat, eicosapentaenoic acid (EPA) are directly available from fish. One other similar fat, alpha-linolenic acid is obtained from vegetable oils and nuts. In two human studies, one fish meal a week was associated with a 60% reduction in the risk of developing Alzheimer's disease. In rodents fed diets enriched with these fats performed better in learning and memory tasks compared with rodents fed control diets. A number of studies have found that the a diet high in these fats resulted in better regulation of nerve excitability, improved capacity for nerve transmission, and reduced oxidative damage. In one study in humans, higher total intake of these fats was significantly associated with a lower risk for Alzheimer's disease. DHA provided the strongest effect, EPA did not show an effect and alpha-linolenic acid was associated with lower risk only among persons with a specific genetic defect. Another similar study in humans, did not find an association between total intake of these fats and risk of Alzheimer's disease.

4 Thus far, no human study has indicated that taking a fish oil capsule is associated with less risk of developing the disease, although several clinical trials are currently in progress to examine the therapeutic effect in patients with Alzheimer's disease. More research needs to be done before we can attribute the findings of these few studies to a causal link. Based on what is currently known, the recommended foods for prevention of Alzheimer s disease are oil-based salad dressings, nuts, seeds, fish, mayonnaise, and eggs. Patients should limit their intake of foods that are high in saturated and trans-unsaturated fats, such as red meats, butter, ice cream, commercially baked products, and some margarines that contain partially hydrogenated oils. PHYSICAL EXERCISE: Physical activity is a valuable part of any overall body wellness plan and is associated with a lower risk of cognitive decline. The studies show that if it is safe for someone to engage in cardiovascular exercise to elevate the heart rate, and they are not at increased risk of falling or injury then there are several measurable benefits of physical exercise. Physical exercise will increase the blood flow to your brain and body, providing additional nourishment while reducing potential dementia risk factors such as high blood pressure, diabetes and high cholesterol. It is ideal to consider physical activities that may also be mentally or socially engaging, such as walking with a friend, golf, taking a dance class, joining an exercise group. This will motivate the person to want to do the activity and it will add social interaction to the exercise, which is beneficial when preventing progression of Alzheimer s disease. Regular physical activity, 60 minutes of aerobic exercise at least three times a week, reduces the risk of cognitive decline, and possibly reduce the risk of Alzheimer's disease and other dementias. So, physical exercise has been shown to both reduce the risk of eventually getting Alzheimer s disease in older adults, and also slowing the progression of Alzheimer s in adults whom already have it. The studies show that regular exercise reduces the amount of amyloid in the blood and brain fluids, which probably means that it is reducing the amount of excess amyloid in brain cells. Studies also show that regular exercise significantly reduces the secondary symptoms of Alzheimer s including agitation, anxiety and depression. Since stroke, or multiple mini-strokes, are the second most common cause of dementia, and often stroke and Alzheimer s occur together,, the combination of a heart smart diet and regular aerobic exercise will reduce the risk of stroke at that same time as it is measurably improving the risk of progression of Alzheimer s disease.

5 BRAIN GAMES: Keeping your mind active in specific ways can make thinking and memory skills less likely to decline. So brain games, puzzles, may help slow memory loss and other mental decline. Studies show that the brain games need to focus on short term memory, reasoning, and speed of processing information. People who do these brain games, also improved at everyday tasks, such as the ability to manage money and do housework. There are a wide variety of brain games and activities available online. The most important thing is that the person enjoys the exercise and that the brain games, keep your brain active and challenged. You don t have to do formal brain games, simple challenges such as learning a new language or musical instrument, crossword puzzles, board games and adult education classes are often all that is required. Researchers believe that keeping your brain active with brain games and tasks, may help build up a reserve supply of brain cells and links between them. You might even grow new brain cells. COFFEE COMPOUNDS: It has been reported by researchers that daily coffee/caffeine intake during mid-life and in older age decreases the risk of Alzheimer's disease. Caffeine has been shown to decrease brain production of the abnormal protein amyloid. Separately, studies in animals have shown that caffeine and another mystery compound in coffee, cause an increase in blood levels of a growth factor called GCSF (granulocyte colony stimulating factor). GCSF is a substance greatly decreased in patients with Alzheimer's disease and demonstrated to improve memory in Alzheimer's mice. Studies are currently underway to use increased GCSF therapy to halt the progression in mild Alzheimer s. The study did not address whether instant freeze dried coffee, has the same effect, as fresh drip coffee. Higher levels of GCSF recruits stem cells to enter the brain and remove the harmful amyloid protein that initiates the disease. GCSF also creates new connections between brain cells and increases the number of new brain cells. Similar studies in humans are expected to published in the near future. The researchers believe that 4-5 cups a day of coffee were necessary to have protection against Alzheimer s. The average American coffee drinker, consumes 1 ½ to 2 cups a day. Even starting to drink this amount of coffee later in life with moderate Alzheimer s is expected to have beneficial effects. Other sources of caffeine, such as carbonated drinks, energy drinks, and tea, will have some benefit, but would not provide the same level of protection against Alzheimer's as coffee, because of the missing mystery component found in coffee.

6 Coffee also contains many ingredients, including ones that have anti-inflammatory effects. An increasing body of research indicates that moderate consumption of coffee decreases the risk of several diseases of aging, including Parkinson's disease, Type II diabetes and stroke. Just within the last few months, new studies have reported that drinking coffee in moderation may also significantly reduce the risk of breast and prostate cancers. ASPIRIN: One baby aspirin (81mg) a day (not a full size aspirin) has been known for years to reduce the risk of both stroke and heart attack by %. It also reduces the risk of colon cancer. However, there is conflicting research about the protective effects of baby aspirin on the risk of getting Alzheimer s or slowing progression of the disease. Older research could not find a benefit from taking daily aspirin for Alzheimer s disease and noted an increased risk of gastrointestinal bleeding. Newer research suggests that there is some measurable benefit due to the anti-inflammatory effects of the aspirin in the brain; and due to aspirin selectively blocking certain enzymes that break amyloid protein in fibrils that cause clumping. Studies have shown an increased risk of the less common form of stroke, known as intra-cerebral hemorrhage, while taking baby aspirin, due to the blood thinning effects of low dose aspirin. At this time the use of daily baby aspirin to specifically prevent or delay the onset of Alzheimer s disease is not recommended. The following is a link to the current US Preventive Medicine Task Force recommendations for use of daily low dose aspirin in different age and sex groups. These recommendations are not based on Alzheimer s disease. Instead, they are based on more well founded studies related to prevention of stroke, heart attack and certain cancers. or-the-prevention-of-cardiovascular-disease-preventive-medication MAGNESIUM: A new study suggests that increasing your intake of magnesium, an essential mineral found in dark leafy vegetables and certain fruits, beans, and nuts, may help combat memory lapses associated with aging. Other research has shown that only about 32% of Americans get the recommended intake of magnesium in their diet. Numerous studies have shown that the brains of Alzheimer s patients at autopsy, have a great deal more aluminum in the hippocampus portion of the brain, than normal people. The

7 hippocampus is involved with memory. Further investigation has determined that this collection of aluminum is due to a deficiency of magnesium. Not just any magnesium will do. Because the magnesium needs to cross the blood brain barrier, and get into the active part of the brain to do its work, some forms of magnesium in our diet are better than others for medical benefits. Research from December 2015 shows that mice feed magnesium threonate had a decrease in the beta amyloid deposition in amyloid plaques. An improvement in cognitive functions were documented. It is not clear how the magnesium threonate is transported across the blood brain barrier. Any magnesium supplement would need to be able to have a measurable portion cross the blood brain barrier, if it is to affect the progression of Alzheimer s. At this time, more research needs to be done. In addition, other forms of magnesium would not be expected to have similar results and may have unpleasant intestinal side effects, like you would get from drinking milk of magnesia. MELATONIN: Melatonin is produced by the pineal gland in the brain. Peak levels of melatonin are released at dusk, and the hormone appears to be instrumental in the series of changes that we call falling asleep. Melatonin levels naturally decrease with age, but people with Alzheimer's disease have especially low levels -- sometimes only half as much as people of the same age who don't have the disease. About 20-45% of Alzheimer's disease patients have disruptions in their sleep and agitation in the early evening, called sundowning. Patients will experience periods of sundowning, usually in the middle stages of the disease. Sundowning takes a toll on those who have Alzheimer's and contributes greatly to caregiver stress and fatigue. It reportedly plays a major role in decisions to move those with Alzheimer's from home care to nursing homes. Melatonin secretion has been shown to be greatly decreased in Alzheimer s disease. 3mg of melatonin at bedtime has been shown to decrease sundowning and larger doses throughout the day have been associated with improvement in sleep, and cognitive and behavioral issues. Further studies in twins and larger groups of patients, suggest that 6mg at bedtime is a safe and appropriate dose to help with sundowning, sleep disturbances, and perhaps behavioral issues in Alzheimer s patients. Thus far, no melatonin-type medications have been developed specifically for Alzheimer's disease or sundowning.

8 OTHERS: Several chemical substances belonging to classes of natural dietary origin display protective properties against Alzheimer's disease. These compounds, known as nutraceuticals, differ structurally, act therefore at different biochemical and metabolic levels and have shown different types of neuroprotective properties. Studies have been done on flavonoids, some vitamins and other natural substances that might be beneficial for the maintenance of a good cognitive performance. Other than those vitamins, fats, and substances discussed above, there is a substantial lack of quality studies to recommend other nutraceuticals for the delay or to halt progression of Alzheimer s. Nevertheless, the strong potential for neuroprotective action from other nutraceuticals warrants further studies in the field.

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